PMID- 32958903
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20211220
IS  - 1748-7838 (Electronic)
IS  - 1001-0602 (Print)
IS  - 1001-0602 (Linking)
VI  - 31
IP  - 2
DP  - 2021 Feb
TI  - RAB31 marks and controls an ESCRT-independent exosome pathway.
PG  - 157-177
LID - 10.1038/s41422-020-00409-1 [doi]
AB  - Exosomes are generated within the multivesicular endosomes (MVEs) as intraluminal 
      vesicles (ILVs) and secreted during the fusion of MVEs with the cell membrane. 
      The mechanisms of exosome biogenesis remain poorly explored. Here we identify 
      that RAB31 marks and controls an ESCRT-independent exosome pathway. Active RAB31, 
      phosphorylated by epidermal growth factor receptor (EGFR), engages flotillin 
      proteins in lipid raft microdomains to drive EGFR entry into MVEs to form ILVs, 
      which is independent of the ESCRT (endosomal sorting complex required for 
      transport) machinery. Active RAB31 interacts with the SPFH domain and drives ILV 
      formation via the Flotillin domain of flotillin proteins. Meanwhile, RAB31 
      recruits GTPase-activating protein TBC1D2B to inactivate RAB7, thereby preventing 
      the fusion of MVEs with lysosomes and enabling the secretion of ILVs as exosomes. 
      These findings establish that RAB31 has dual functions in the biogenesis of 
      exosomes: driving ILVs formation and suppressing MVEs degradation, providing an 
      exquisite framework to better understand exosome biogenesis.
FAU - Wei, Denghui
AU  - Wei D
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 
      510060, China.
FAU - Zhan, Weixiang
AU  - Zhan W
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 
      510060, China.
FAU - Gao, Ying
AU  - Gao Y
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 
      510060, China.
FAU - Huang, Liyan
AU  - Huang L
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 
      510060, China.
FAU - Gong, Run
AU  - Gong R
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 
      510060, China.
FAU - Wang, Wen
AU  - Wang W
AD  - Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated 
      Hospital of Sun Yat-sen University, Zhuhai, Guangdong, 519000, China.
FAU - Zhang, Ruhua
AU  - Zhang R
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 
      510060, China.
FAU - Wu, Yuanzhong
AU  - Wu Y
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 
      510060, China.
FAU - Gao, Song
AU  - Gao S
AUID- ORCID: 0000-0001-7427-6681
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 
      510060, China.
FAU - Kang, Tiebang
AU  - Kang T
AUID- ORCID: 0000-0001-8805-4174
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 
      510060, China. kangtb@sysucc.org.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200921
PL  - England
TA  - Cell Res
JT  - Cell research
JID - 9425763
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (Membrane Proteins)
RN  - 0 (RAB31 protein, human)
RN  - 0 (flotillins)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
SB  - IM
CIN - Cell Res. 2021 Feb;31(2):105-106. PMID: 32973340
MH  - Cell Membrane/metabolism
MH  - Endosomal Sorting Complexes Required for Transport/*metabolism
MH  - ErbB Receptors/metabolism
MH  - Exosomes/*metabolism
MH  - Gene Knockdown Techniques/methods
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Lysosomes/metabolism
MH  - Membrane Proteins/chemistry/genetics/metabolism
MH  - Monomeric GTP-Binding Proteins/metabolism
MH  - Multivesicular Bodies/metabolism
MH  - Protein Domains
MH  - Signal Transduction/*genetics
MH  - Transfection
MH  - rab GTP-Binding Proteins/genetics/*metabolism
PMC - PMC8027411
COIS- The authors declare no competing interests.
EDAT- 2020/09/23 06:00
MHDA- 2021/12/21 06:00
PMCR- 2020/09/21
CRDT- 2020/09/22 05:40
PHST- 2020/03/18 00:00 [received]
PHST- 2020/08/17 00:00 [accepted]
PHST- 2020/09/23 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2020/09/22 05:40 [entrez]
PHST- 2020/09/21 00:00 [pmc-release]
AID - 10.1038/s41422-020-00409-1 [pii]
AID - 409 [pii]
AID - 10.1038/s41422-020-00409-1 [doi]
PST - ppublish
SO  - Cell Res. 2021 Feb;31(2):157-177. doi: 10.1038/s41422-020-00409-1. Epub 2020 Sep 
      21.